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HWDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOGY III 



cell type. Since about 30 per cent of the brain lipids 

 arc associated with mitochondria and most of the 

 RXA with microsomes (4), the interesting possibility 

 offers itself that the Deiter's cells, among the largest 

 of neurons, are richest in mitochondria and micro- 

 somes. Purkinje cells would, then, have somewhat 

 fewer mitochondria and considerably less microsomes, 

 while spinal ganglia would contain the least of both 

 particulates. Such speculation is not in conflict with 

 observations from other sources concerning the 

 respiratory metabolism of these cells. 



With the loss of function during degeneration of 

 the severed peripheral nerve, there are a series of 

 characteristic changes which have provided some 

 important clues to the understanding of neuronal 

 metabolism. After nerve section certain nonspecific 

 phosphatases decreased rapidly until the 16th day 

 following section, while nucleotidase and j3-glu- 

 curonidase increased considerably after either nerve 

 section or crush, the RNA increasing at a greater 

 rate than the DNA (58, 59). Phospholipids remain 

 unchanged after either section or crush until the 8th 

 day when they began to rapidly decrease (77). While 

 the phospholipid continued to decrease in the sec- 

 tioned nerve after 30 days, it began to gradually 

 increase in the crushed nerve throughout the period 

 of regeneration when remyelinization was occurring. 

 These results are indicative of the fact that protein, 

 lipid and nucleic acid breakdown and synthesis do 

 occur in adult neural tissue and at a surprisingly 

 rapid rate. The inability to demonstrate noncarbo- 

 hydrate pathways of metabolism in neural tissue 

 in vitro is particularly acute in the light of such studies. 

 Perhaps the metabolic processes during Wallerian 

 degeneration involve a transient reversion to the 

 embryonic development of peripheral nerve, and 

 with regeneration completed the enzymatic processes, 

 initially elaborated by the RNA and DNA of pro- 

 liferating Schwann cells, become dormant once more. 

 I In importanl fact is that neural tissue docs contain 

 such metabolic systems that can be called into play 

 to suit its requirements. Very likely these processes are 

 under the control of certain regulatory mechanisms 

 which in turn are responsive to particular physico 

 chemical stimuli, Mich ,ts trauma and excitatorv 

 .niivitv. In all cells throughout the organism, en- 

 zymes and structural components are constantly 

 being resynthesized and, although mitotic activity in 

 the neurons presumably ceases after maturation of 

 the neuroblast, neural tissue must certainly be no 

 ption Protein synthesis proceeds at a rapid rate 



even in the adult brain, as indicated by experiments 

 with methionine-S 35 (36). 



Insofar as long axons may contain a thousand times 

 as much protoplasm as the cell soma, during axonal 

 regeneration the soma must produce several times its 

 protoplasmic volume per day (45) Among the most 

 challenging problems of ncurochemistry is that 

 concerned with the factors initiating and regulating 

 the regenerative processes of the dissevered axon. 

 Numerous explanations have been offered for neuro- 

 genesis and, although the discussion is beyond the 

 scope of this chapter, it is important to mention some 

 of the neurotropic substances that are presumably 

 involved, fragments of mouse sarcoma, but not of 

 brain or liver, were found to stimulate selectively the 

 growth and differentiation of sympathetic and sensory 

 neurons (74). Chemical isolation and characterization 

 of the neurotropic agent revealed the following 

 composition: 66 per cent protein, 27 per cent RNA 

 and 0.2 per cent DNA. The agent, therefore, is either 

 a specific protein associated with microsomal RNA 

 or, if it is RNA, it must be a particular form of the 

 nucleic acid found in sarcoma but not in normal 

 brain or liver. The observation that neuronal growth 

 and proliferation in the mesencephalic nucleus of 

 amphibians increased abruptly during metamorphosis 

 led to the finding that thyroxine was the agent 

 responsible for this sudden maturation (72). The 

 collateral branching of the intact uninjured nerve 

 occurring after the innervated muscle is rendered 

 paretic has been attributed to the elaboration of a 

 substance containing unsaturated (glyceride) fatty 

 acids (20). The facilitation of neuronal growth in 

 tissue cultures by cortisone (40, 40a) and of nerve re- 

 generation in the transected spinal cord by Piromen 

 (a bacterial polysaccharide) (40,40a! have led to the 

 development of the notion that nerve regeneration is 

 normally prevented by glial proliferation which is 

 presumably inhibited by these substances. 



The numerous and unique structural changes 

 occurring in the axoplasm and cell body during 

 growth and differentiation provide a fruitful basis for 

 approaching the problem of neural function in 

 relation to chemistry. Perhaps the most important 

 structures to undergo disintegration alter section of 

 the axon are the neurofibrils which presumably 

 constitute the core of the conductive apparatus ( 102 1. 

 I he surrounding 'neuroplasm,' meanwhile, establishes 

 Contact with elements of the neurilemmal sheath and 



eventually forms the protoplasmic bands of Beungner 



which constitute the framework for the neurofibrils 

 during regeneration (14, 94). Protoplasm is eon- 



